Effect of endothelin-1 and its combination with adenosine on myocardial contractility and myocardial energy metabolism in vivo

Contradictory results have been reported about the isotropic effects of the vasoconstrictive peptide endothelia-1 (ET-1). In contrast to in vitro experiments in vivo studies could not demonstrate a positive inotropy of ET-1. It may be possible, that the direct positive isotropic effect of ET-1 obser...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 1995-09, Vol.27 (9), p.1989-1997
Main Authors: Beyer, Martin E., Nerz, Stefan, Kazmaier, Silke, Hoffmeister, Hans Martin
Format: Article
Language:English
Subjects:
Adenosine
Adenosine - pharmacology
Animals
Drug Combinations
Endothelin-1
Endothelins - pharmacology
Energy Metabolism - drug effects
Heart - physiology
Hemodynamics - drug effects
High-energy phosphates
Isotropic effects
Isovolumic measurements
Male
Myocardial Contraction - drug effects
Rats
Rats, Wistar
Vasodilator Agents - pharmacology
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Summary:Contradictory results have been reported about the isotropic effects of the vasoconstrictive peptide endothelia-1 (ET-1). In contrast to in vitro experiments in vivo studies could not demonstrate a positive inotropy of ET-1. It may be possible, that the direct positive isotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropy due to its coronar-constrictive effect. This study examined the hemodynamic and isotropic effects of 2500 ng ET-1/kg without and after pretreatment with the vasodilating nucleoside adenosine (0.5. 2.0, 5.0 mg ADO/kg/min). Data were compared with NaCl controls in open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation isovolumic measurements were carried out for quantification of myocardial contractility independently of peripheral vascular effects. We further examined the effect of ET-1 and its combination with 2.0 mg ADO/kg/min on myocardial high-energy phosphates (ATP. AMP. ADP, creatine phosphate). ET-1 causes a strong and longlasting vasoconstriction (+ 186% v preinfusion values), which is dose-dependently antagonized in part by ADO (+ 109%, + 1361%. + 60%). While the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/d t max (peak dP/d t max) were unchanged with sole ET-1 (peak LVSP: + 5%, peak dP/d t max −2%). these indexes of myocardial contractility were increased after pretreatment with ADO (peak LVSP: + 11%, + 13%, + 4%; peak dP/d t max: +9%, + 20%, + 10%) indicating a positive isotropic effect of ET-1, ET-1 causes a reduction of the high energy-phosphates (ATP: −19%, P
ISSN:0022-2828
1095-8584
DOI:10.1016/0022-2828(95)90020-9